Cyclopropanecarbonyl chloride → N-[5-[{4-fluoro-3-[(trifluoroacetyl)amino]phenyl}(methyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide

HRID 1800638Notes

Reaction equation

HRID 1800638 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[C:9]([N:10]=1)=[CH:8][CH:7]=[C:6]([N:11]([CH3:26])[C:12]1[CH:13]=[CH:14][C:15]([F:25])=[C:16]([NH:18][C:19](=[O:24])[C:20]([F:23])([F:22])[F:21])[CH:17]=1)[N:5]=2.[CH:27]1([C:30](Cl)=[O:31])[CH2:29][CH2:28]1>N1C=CC=CC=1>[F:25][C:15]1[CH:14]=[CH:13][C:12]([N:11]([CH3:26])[C:6]2[N:5]=[C:4]3[S:3][C:2]([NH:1][C:30]([CH:27]4[CH2:29][CH2:28]4)=[O:31])=[N:10][C:9]3=[CH:8][CH:7]=2)=[CH:17][C:16]=1[NH:18][C:19](=[O:24])[C:20]([F:22])([F:21])[F:23]

Participants

4

Reactant 2

HCID 77637Cyclopropanecarbonyl chlorideHCID 86646057N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)(methyl)amino]-2-fluorophenyl)-2,2,2-trifluoroacetamide

Product 1

HCID 86646058N-[5-[{4-fluoro-3-[(trifluoroacetyl)amino]phenyl}(methyl)amino][1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamideYield 59%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)(methyl)amino]-2-fluorophenyl}-2,2,2-trifluoroacetamide (385 mg, 1.00 mmol) in pyridine (10 mL) was added cyclopropanecarbonyl chloride (144 μL, 1.60 mmol) at 4° C., and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, and the residue was suspended in ethyl acetate (10 mL). The obtained suspension was washed with saturated aqueous sodium hydrogen carbonate solution (10 mL) and saturated brine (10 mL), and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=80/20→0/100), and the obtained solution was concentrated under reduced pressure to give the title compound (250 mg, 59%) as a colorless powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. washThe obtained suspension was washed with saturated aqueous sodium hydrogen carbonate solution (10 mL) and saturated brine (10 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationThe insoluble material was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=80/20→0/100)
  7. concentrationthe obtained solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-519d645576d54639a5df0c317b3eeaec
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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